Cesium carbonate → Methyl 2-isobutyl-5-[4-(methylsulfonyl)phenoxy]-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

HRID 1177368Notes

Reaction equation

HRID 1177368 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:7]2=[O:16].[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28](F)=[CH:27][CH:26]=1)(=[O:24])=[O:23].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.[Cu]I>[CH2:17]([N:6]1[CH2:5][CH2:4][C:3]2[C:8](=[CH:9][C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:11][C:2]=2[O:1][C:28]2[CH:29]=[CH:30][C:25]([S:22]([CH3:21])(=[O:24])=[O:23])=[CH:26][CH:27]=2)[C:7]1=[O:16])[CH:18]([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 679941-Fluoro-4-(methylsulphonyl)benzeneHCID 59560203Methyl 5-hydroxy-2-isobutyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

Product 1

HCID 59559916Methyl 2-isobutyl-5-[4-(methylsulfonyl)phenoxy]-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 5-hydroxy-2-isobutyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (250 mg, 0.90 mmol), 4-fluorophenyl methyl sulfone (236 mg, 1.35 mmol), Cs2CO3 (441 mg, 1.35 mmol) and CuI (100 mg, 1 mmol) in DMF (20 mL) was heated to 100° C. for 4 hours. The solvent was removed under reduced pressure. The residue was poured into water (20 mL) and extracted with EtOAc (50 mL×2). The combined organic layers was washed with brine (20 mL×2), dried over Na2SO4 and concentrated. The product was purified via column chromatography on silica gel eluted with 10-30% EtOAc in hexanes to afford the ether (312 mg, 78%) as a white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.97 (d, J=6.78 Hz, 6 H) 1.94-2.16 (m, 1 H) 2.94 (t, J=6.59 Hz, 2 H) 3.04-3.16 (m, 3 H) 3.41 (d, J=7.54 Hz, 2 H) 3.55 (t, J=6.59 Hz, 2 H) 3.87-4.01 (m, 3 H) 7.00-7.11 (m, 2 H) 7.80 (d, J=1.70 Hz, 1 H) 7.88-8.00 (m, 2H) 8.66 (d, J=1.51 Hz, 1 H); MS (ESI, pos): 432.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionThe residue was poured into water (20 mL)
  3. extractionextracted with EtOAc (50 mL×2)
  4. washThe combined organic layers was washed with brine (20 mL×2)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe product was purified via column chromatography on silica gel
  8. washeluted with 10-30% EtOAc in hexanes
  9. customto afford the ether (312 mg, 78%) as a white solid

Sources & evidence

ORD record
ord-329e67d4a8c54bf6917deaefb268642e
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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